Project Summary/Abstract Long-acting injectable antiretroviral therapy (LAI-ART) represents the next innovation in HIV pharmacotherapy and offers enormous promise to minimize challenges to daily oral ART, increase suboptimal rates of virologic suppression in the United States (U.S.), and maximize the ability to end the HIV epidemic. The regimen recently found non-inferior to oral ART in Phase 3 efficacy trials consists of a an intramuscular injection of two antiretrovirals, cabotegravir and rilpivirine, given at 4-week intervals after patients have achieved virologic suppression on oral therapy. In order to translate the promising efficacy of this novel drug platform into real world effectiveness, implementation science is necessary before, during, and after introduction of the product, particularly in clinics serving vulnerable urban HIV populations, as innovations are often delayed in reaching these groups. Implementation research on LAI-ART can identify barriers and bottlenecks to adoption and use to help ensure equitable utilization. LAI-ART holds appeal for at least two groups of patients: 1) those with a history of adherence challenges for whom the extended dosing interval could mitigate psychosocial and structural barriers to daily oral ART; 2) already adherent patients for whom LAI-ART could improve quality of life. Yet without the benefit of a clinic system to support retention, providers may hesitate to use or even withhold LAI-ART from patients who have struggled with adherence to care because of the possibility of drug resistance and viral rebound if doses are missed. For patients on stable oral regimens, clinic burden increases because of an increase in visit frequency to monthly from every 4-12 months. Clinics need systems that support both kinds of patients, but the key features of these care delivery systems are as of yet unknown. This application proposes to comprehensively address the knowledge gap of how best to implement LAI-ART in a way that meets the needs of patients, providers, and clinics in key urban settings using a mixed-methods, multi-level study structured by the Consolidated Framework for Implementation Research (CFIR). Leveraging the expertise of a multidisciplinary team and working in three HIV clinics in high priority Ending the Epidemic jurisdictions (San Francisco, Chicago, and Atlanta) we propose the following specific aims: 1) Evaluate the LAI- ART implementation cascade in three urban HIV clinics; 2) Identify preferred attributes of LAI-ART care delivery among patients and providers; 3) Develop an evidence informed LAI-ART care delivery model to optimize real-world implementation. The proposed research will result in implementation strategies to guide the equitable use of LAI-ART and contribute to Ending the Epidemic efforts in the U.S.